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Frontiers in Pharmacology 2020Peripheral nerve entrapment syndromes commonly result in pain, discomfort, and ensuing sensory and motor impairment. Many conservative measures have been proposed as...
Peripheral nerve entrapment syndromes commonly result in pain, discomfort, and ensuing sensory and motor impairment. Many conservative measures have been proposed as treatment, local injection being one of those measures. Now with high-resolution ultrasound, anatomical details can be visualized allowing diagnosis and more accurate injection treatment. Ultrasound-guided injection technique using a range of injectates to mechanically release and decompress the entrapped nerves has therefore developed called hydrodissection or perineural injection therapy. Several different injectates from normal saline, local anesthetics, corticosteroids, 5% dextrose in water (D5W), and platelet-rich plasma (PRP) are available and present clinical challenges when selecting agents regarding effectiveness and safety. To systematically search and summarize the clinical evidence and mechanism of different commonly used injectates for ultrasound-guided hydrodissection entrapment neuropathy treatment. Four databases, including PubMed, EMBASE, Scopus, and Cochrane were systematically searched from the inception of the database up to August 22, 2020. Studies evaluating the effectiveness and safety of different commonly used injectates for ultrasound-guided hydrodissection entrapment neuropathy treatment were included. Injectate efficacy presents clinical effects on pain intensity, clinical symptoms/function, and physical performance, electrodiagnostic findings, and nerve cross-sectional areas. Safety outcomes and mechanism of action of each injectate were also described. From ten ultrasound-guided hydrodissection studies, nine studies were conducted in carpal tunnel syndrome and one study was performed in ulnar neuropathy at the elbow. All studies compared different interventions with different comparisons. Injectates included normal saline, D5W, corticosteroids, local anesthetics, hyaluronidase, and PRP. Five studies investigated PRP or PRP plus splinting comparisons. Both D5W and PRP showed a consistently favorable outcome than those in the control group or corticosteroids. The improved outcomes were also observed in comparison groups using injections with normal saline, local anesthetics, or corticosteroids, or splinting. No serious adverse events were reported. Local steroid injection side effects were reported in only one study. Ultrasound-guided hydrodissection is a safe and effective treatment for peripheral nerve entrapment. Injectate selection should be considered based on the injectate mechanism, effectiveness, and safety profile.
PubMed: 33746745
DOI: 10.3389/fphar.2020.621150 -
International Braz J Urol : Official... 2021Squamous cell carcinoma (SCC) of the penis is a rare disease in developed countries but is associated with significant morbidity and mortality. A crucial prognostic... (Review)
Review
PURPOSE
Squamous cell carcinoma (SCC) of the penis is a rare disease in developed countries but is associated with significant morbidity and mortality. A crucial prognostic factor is the presence of inguinal lymph node metastases (ILNM) at the time of diagnosis. At least 25% of cases have micrometastases at the time of diagnosis. Therefore, we performed a literature review of studies evaluating factors, both clinical and pathological, predictive of lymph node metastases in penile SCC.
MATERIALS AND METHODS
Studies were identified using PubMed and search terms included the following: penile cancer, penile tumor, penile neoplasm, penile squamous cell carcinoma, inguinal lymph node metastasis, lymph node metastases, nodal metastasis, inguinal node metastasis, inguinal lymph node involvement, predictors, and predictive factor. The number of patients and predictive factors were identified for each study based on OR, HR, or RR in multivariate analyses, as well as their respective significance values. These were compiled to generate a single body of evidence supportive of factors predictive of ILNM in penile SCC.
RESULTS
We identified 31 studies, both original articles and meta-analyses, which identified factors predictive of metastases in penile SCC. The following clinical factors were predictive of ILNM in penile SCC: lymphovascular invasion (LVI), increased grade, increased stage (both clinical and pathological), infiltrative and reticular invasion, increased depth of invasion, perineural invasion, and younger patient age at diagnosis. Biochemically, overexpression of p53, SOD2, Ki-67, and ID1 were associated with spread of SCC to inguinal lymph nodes. Diffuse PD-L1 expression, increased SCC-Ag expression, increased NLR, and CRP >20 were also associated with increased ILNM.
CONCLUSIONS
A multitude of factors are associated with metastasis of SCC of the penis to inguinal lymph nodes, which is associated with poor clinical outcomes. The above factors, most strongly LVI, grade, and node positivity, may be considered when constructing a nomogram to risk-stratify patients and determine eligibility for prophylactic inguinal lymphadenectomy.
Topics: Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Penile Neoplasms; Prognosis
PubMed: 33650835
DOI: 10.1590/S1677-5538.IBJU.2020.0959 -
Therapeutic Advances in... 2021Data on prognostic factors associated with outcome following resection of perihilar cholangiocarcinoma vary. We sought to define and characterize current available...
Data on prognostic factors associated with outcome following resection of perihilar cholangiocarcinoma vary. We sought to define and characterize current available evidence on prognostic factors associated with perihilar cholangiocarcinoma after resection. The PubMed, Embase, and Cochrane library were systematically searched for relevant studies published before December 2019. Prognostic factors were identified from multivariate regression analyses in studies. Only high-quality studies were included (Newcastle-Ottawa Scale > 6 stars). A total of 45 studies involving 7338 patients were analyzed. The meta-analysis demonstrated that serum bilirubin levels (hazard ratio: 1.76, 95% confidence interval: 1.27-2.44), serum CA19-9 levels (hazard ratio: 1.32, 95% confidence interval: 1.05-1.65), tumor size (hazard ratio: 1.27, 95% confidence interval: 1.04-1.55), major vascular involvement (hazard ratio: 1.61, 95% confidence interval: 1.09-2.38), distance metastasis (hazard ratio: 17.60, 95% confidence interval: 2.01-154.09), perioperative blood transfusion (hazard ratio: 1.36, 95% confidence interval: 1.15-1.62), T-stage (hazard ratio: 1.96, 95% confidence interval: 1.47-2.61), lymph node metastasis (hazard ratio: 2.06, 1.83-2.31), resection margin status (hazard ratio: 2.34, 95% confidence interval: 1.89-2.89), not-well histology differentiation (hazard ratio: 2.03, 95% confidence interval: 1.69-2.44), perineural invasion (hazard ratio: 2.37, 95% confidence interval: 1.59-3.55), and lymphovascular invasion (hazard ratio: 1.41, 95% confidence interval: 1.15-1.73) were prognostic factors for poorer overall survival. Adjuvant chemotherapy (hazard ratio: 0.37, 95% confidence interval: 0.25-0.55) had a positive effect on prolonged overall survival. In addition, positive resection margin status (hazard ratio: 1.96, 95% confidence interval: 1.47-2.61) and lymph node metastasis (hazard ratio: 2.06, 95% confidence interval: 1.83-2.31) were associated with poorer disease-free survival. The prognostic factors identified in the present meta-analysis can be used to characterize patients in clinical practice and enrich prognostic tools, which could be included in future trial designs and generate hypotheses to be tested in future research to promote personalized treatment.
PubMed: 33629062
DOI: 10.1177/2631774521993065 -
Medicina Oral, Patologia Oral Y Cirugia... Mar 2021The immunohistochemical expression of vascular endothelial growth factor is a prognostic marker in several cancer types. In salivary gland tumors, the association... (Meta-Analysis)
Meta-Analysis
Prognostic value of the immunohistochemical expression of vascular endothelial growth factors in malignant salivary gland neoplasms: a systematic review and meta-analysis.
BACKGROUND
The immunohistochemical expression of vascular endothelial growth factor is a prognostic marker in several cancer types. In salivary gland tumors, the association between vascular endothelial growth factor and prognosis remains unclear. The purpose of this study was to perform a systematic review and meta-analysis to assess whether the immunohistochemical expression of vascular endothelial growth factor in patients with salivary gland neoplasms presents prognostic value.
MATERIAL AND METHODS
Immunohistochemical studies assessing the predictive value of vascular endothelial growth factor in salivary gland neoplasms were systematically reviewed using PubMed, Scopus, Embase, Cochrane Library, and Web of Science databases. It was assessed any survival rates. The fixed-effect model with an adjusted hazard ratio (HR) and 95% confidence intervals (95% CI) as effect measures were performed in the meta-analysis. The Quality in Prognosis Studies (QUIPS) tool was used to assess the quality of the included studies, and the evidence quality was assessed by the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system.
RESULTS
The immunohistochemical overexpression of vascular endothelial growth factor in patients with salivary gland neoplasms was associated with shortened survival (HR=5.37, 95% CI: 2.67-10.83, P = 0.00001). In addition, the presence of vascular endothelial growth factor was tightly associated with tumor size, lymph node metastasis, clinical stage, perineural invasion, vascular invasion, poor local control of the disease, and recurrence.
CONCLUSIONS
The immunohistochemical overexpression of vascular endothelial growth factor in patients with salivary gland neoplasms has prognostic value and was associated with decreased survival time. However, more primary well-designed studies are necessary to increase the level of evidence.
Topics: Biomarkers, Tumor; Humans; Neoplasm Recurrence, Local; Prognosis; Salivary Gland Neoplasms; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 33609023
DOI: 10.4317/medoral.23974 -
Anesthesiology Feb 2021Liposomal bupivacaine is purported to extend analgesia of peripheral nerve blocks when administered perineurally. However, evidence of the clinical effectiveness of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Liposomal bupivacaine is purported to extend analgesia of peripheral nerve blocks when administered perineurally. However, evidence of the clinical effectiveness of perineural liposomal bupivacaine is mixed. This meta-analysis seeks to evaluate the effectiveness of perineural liposomal bupivacaine in improving peripheral nerve block analgesia as compared with nonliposomal local anesthetics.
METHODS
The authors identified randomized trials evaluating the effectiveness of peripheral nerve block analgesic that compared liposomal bupivacaine with nonliposomal local anesthetics. The primary outcome was the difference in area under the receiver operating characteristics curve (AUC) of the pooled 24- to 72-h rest pain severity scores. Secondary outcomes included postoperative analgesic consumption, time to first analgesic request, incidence of opioid-related side effects, patient satisfaction, length of hospital stay, liposomal bupivacaine side effects, and functional recovery. AUC pain scores were interpreted in light of a minimal clinically important difference of 2.0 cm · h.
RESULTS
Nine trials (619 patients) were analyzed. When all trials were pooled, AUC pain scores ± SD at 24 to 72 h were 7.6 ± 4.9 cm · h and 6.6 ± 4.6 cm · h for nonliposomal and liposomal bupivacaine, respectively. As such, perineural liposomal bupivacaine provided a clinically unimportant benefit by improving the AUC (95% CI) of 24- to 72-h pain scores by 1.0 cm · h (0.5 to 1.6; P = 0.003) compared with nonliposomal bupivacaine. Excluding an industry-sponsored trial rendered the difference between the groups nonsignificant (0.7 cm · h [-0.1 to 1.5]; P = 0.100). Secondary outcome analysis did not uncover any additional benefits to liposomal bupivacaine in pain severity at individual timepoints up to 72 h, analgesic consumption, time to first analgesic request, opioid-related side effects, patient satisfaction, length of hospital stay, and functional recovery. No liposomal bupivacaine side effects were reported.
CONCLUSIONS
Perineural liposomal bupivacaine provided a statistically significant but clinically unimportant improvement in the AUC of postoperative pain scores compared with plain local anesthetic. Furthermore, this benefit was rendered nonsignificant after excluding an industry-sponsored trial, and liposomal bupivacaine was found to be not different from plain local anesthetics for postoperative pain and all other analgesic and functional outcomes. High-quality evidence does not support the use of perineural liposomal bupivacaine over nonliposomal bupivacaine for peripheral nerve blocks.
Topics: Analgesia; Anesthetics, Local; Bupivacaine; Humans; Liposomes; Nerve Block; Pain Management; Peripheral Nerves; Treatment Outcome
PubMed: 33372953
DOI: 10.1097/ALN.0000000000003651 -
Frontiers in Oncology 2020The progression and clinical course of head and neck squamous cell carcinoma (HNSCC) relies on complex interactions between cancer and stromal cells in the tumor...
INTRODUCTION
The progression and clinical course of head and neck squamous cell carcinoma (HNSCC) relies on complex interactions between cancer and stromal cells in the tumor microenvironment (TME). Among the most abundant of these stromal cells are cancer-associated fibroblasts (CAFs). While their contribution to tumor progression is widely acknowledged, and various CAF-targeted treatments are under development, the relationship between CAF density and the clinicopathologic course of HNSCC has not been clearly defined. Here we examine the published evidence investigating the relationship of cancer-associated fibroblasts to local recurrence and indicators of prognostic significance in HNSCC.
METHODS
We conducted a meta-analysis of existing publications that compare the relationship between CAF density, local recurrence, and clinically significant pathologic criteria of disease development (T stage, nodal positivity, clinical stage, vascular invasion, perineural invasion, Ki67 expression, and differentiation). Thirteen studies met the selection criteria, providing a total study population of 926 patients. Forest plots and risk ratios were generated to illustrate overall relationships.
RESULTS
Higher CAF density within the tumor microenvironment is associated with advanced T stage, nodal infiltration, clinical stage, vascular invasion, perineural invasion, Ki67 expression, and differentiation (p <0.05). High CAF density is also associated with increased rates of local recurrence (p <0.001).
CONCLUSIONS
Across multiple studies, increased CAF density is correlated with histopathological criteria of poor prognosis in HNSCC. These findings highlight that CAFs may play a pivotal role in HNSCC development and progression. Staining for CAFs may represent a valuable addition to current pathologic analysis and help to guide prognosis and treatment. Understanding the mechanisms by which CAFs reciprocally interact with cancer cells will be crucial for optimization of TME-focused treatment of HNSCC.
PubMed: 33330034
DOI: 10.3389/fonc.2020.565306 -
Anaesthesia Jul 2021Both perineural and intravenous dexamethasone and dexmedetomidine are used as local anaesthetic adjuncts to enhance peripheral nerve block characteristics. However, the... (Meta-Analysis)
Meta-Analysis
Both perineural and intravenous dexamethasone and dexmedetomidine are used as local anaesthetic adjuncts to enhance peripheral nerve block characteristics. However, the effects of dexamethasone and dexmedetomidine based on their administration routes have not been directly compared, and the relative extent to which each adjunct prolongs sensory blockade remains unclear. This network meta-analysis sought to compare and rank the effects of perineural and intravenous dexamethasone and dexmedetomidine as supraclavicular block adjuncts. We sought randomised trials investigating the effects of adding perineural and intravenous dexamethasone or dexmedetomidine to long-acting local anaesthetics on supraclavicular block characteristics, including time to block onset and durations of sensory, motor and analgesic blockade. Data were compared and ranked according to relative effectiveness for each outcome. Our primary outcome was sensory block duration, with a 2-h difference considered clinically important. We performed a frequentist analysis, using the GRADE framework to appraise evidence. One-hundred trials (5728 patients) were included. Expressed as mean (95%CI), the control group (local anaesthetic alone) had a duration of sensory block of 401 (366-435) min, motor block duration of 369 (330-408) min and analgesic duration of 435 (386-483) min. Compared with control, sensory block was prolonged most by intravenous dexamethasone [mean difference (95%CI) 477 (160-795) min], followed by perineural dexamethasone [411 (343-480) min] and perineural dexmedetomidine [284 (235-333) min]. Motor block was prolonged most by perineural dexamethasone [mean difference (95%CI) 294 (236-352) min], followed by intravenous dexamethasone [289 (129-448)min] and perineural dexmedetomidine [258 (212-304)min]. Analgesic duration was prolonged most by perineural dexamethasone [mean difference (95%CI) 518 (448-589) min], followed by intravenous dexamethasone [478 (277-679) min] and perineural dexmedetomidine [318 (266-371) min]. Intravenous dexmedetomidine did not prolong sensory, motor or analgesic block durations. No major network inconsistencies were found. The quality of evidence for intravenous dexamethasone, perineural dexamethasone and perineural dexmedetomidine for prolongation of supraclavicular sensory block duration was 'low', 'very low' and 'low', respectively. Regardless of route, dexamethasone as an adjunct prolonged the durations of sensory and analgesic blockade to a greater extent than dexmedetomidine. Differences in block characteristics between perineural and intravenous dexamethasone were not clinically important. Intravenous dexmedetomidine did not affect block characteristics.
Topics: Adjuvants, Anesthesia; Administration, Intravenous; Anesthetics, Local; Brachial Plexus Block; Dexamethasone; Dexmedetomidine; Humans; Network Meta-Analysis
PubMed: 33118163
DOI: 10.1111/anae.15288 -
PloS One 2020Femoral nerve block (FNB) is one of the first-line analgesic methods for patients following lower extremity surgery. However, FNB with local anesthetics alone exert... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Femoral nerve block (FNB) is one of the first-line analgesic methods for patients following lower extremity surgery. However, FNB with local anesthetics alone exert limited potency and supplemental opioids are often required. Dexmedetomidine (DEX) has been used to improve the analgesic effects of FNB. The present systematic review and meta-analysis were conducted to evaluate the effectiveness of DEX as an adjuvant to local anesthetics for FNB.
METHODS
Randomized controlled trials comparing the effects of DEX versus sham control in combination with local anesthetics for FNB were included in this meta-analysis. Postoperative pain scores, duration of analgesic effects, and postoperative narcotic consumption were outcomes of interest. This research was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements.
RESULTS
A total of 9 studies encompassing 580 participants were included for data synthesis after critical evaluation. DEX as an adjuvant with local anesthetics for FNB significantly relieved pain intensity at 12, 24 and 48 hours after surgery, both at rest (standardized mean difference -1.34 [95% CI -1.87 to -0.82], P<0.00001 at 12 h; -1.26 [-1.90 to -0.0.63], P<0.0001 at 24 h; and -1.34; [-2.18 to -0.50], P = 0.002 at 48 h) and with movement (-1.30 [-2.17 to -0.43], P = 0.004 at 12 h; -1.02 [-1.31 to -0.72], P<0.00001 at 24h; and -1.33 [-2.03 to -0.63], P = 0.0002); it also significantly prolonged analgesic duration (mean difference 7.23 h [95% CI 4.07 to 10.39], P<0.00001) and decreased opioid consumption (mean difference of morphine equivalent -12.13 mg [95% CI -23.36 to -0.89], P<0.00001). Regarding safety, DEX use increased the rate of hypotension (odds ratio 4.10, 95% CI 1.40 to 12.01, P = 0.01).
CONCLUSION
DEX as an adjuvant to local anesthetics for FNB improves analgesia, prolongs analgesic duration and reduces supplemental opioid consumption; but increases hypotension.
Topics: Analgesia; Analgesics, Non-Narcotic; Chemotherapy, Adjuvant; Dexmedetomidine; Female; Humans; Lower Extremity; Male; Nerve Block; Pain Management; Randomized Controlled Trials as Topic
PubMed: 33075089
DOI: 10.1371/journal.pone.0240561 -
PloS One 2020In this study, we sought to identify the potential impacts of disease characteristics on the prognosis of cutaneous squamous cell carcinoma (cSCC). We searched the... (Meta-Analysis)
Meta-Analysis
In this study, we sought to identify the potential impacts of disease characteristics on the prognosis of cutaneous squamous cell carcinoma (cSCC). We searched the PubMed, EmBase, and Cochrane Library databases from their inception until February 2020 to identify studies that investigated the prognosis of cSCC. The pooled effect estimates were applied using odds ratios (OR) and 95% confidence intervals (CI) and were calculated using the random-effects model. Forty-three studies including a total of 21,530 patients and reporting 28,627 cases of cSCC were selected for the final meta-analysis. Poor differentiation (OR, 3.54; 95% CI, 2.30-5.46; P < 0.001), perineural invasion (OR, 3.27; 95% CI, 1.60-6.67; P = 0.001), Breslow greater than 2 mm (OR, 5.47; 95% CI, 2.63-11.37; P < 0.001), diameter greater than 20 mm (OR, 4.62; 95% CI, 2.95-7.23; P < 0.001), and location on temple (OR, 3.20; 95% CI, 1.12-9.15; P = 0.030) were associated with an increased risk of recurrence, whereas immunosuppression status and location on cheek, ear, or lip were not associated with the risk of recurrence. Poor differentiation (OR, 6.82; 95% CI, 4.66-9.99; P < 0.001); perineural invasion (OR, 7.15; 95% CI, 4.73-10.83; P < 0.001); Breslow greater than 2 mm (OR, 6.11; 95% CI, 4.05-9.21; P < 0.001); diameter greater than 20 mm (OR, 5.01; 95% CI, 2.56-9.80; P < 0.001); and location on ear (OR, 2.38; 95% CI, 1.39-4.09; P = 0.002), lip (OR, 2.15; 95% CI, 1.26-3.68; P = 0.005), and temple (OR, 2.77; 95% CI, 1.20-6.40; P = 0.017) were associated with an increased risk of metastasis, whereas immunosuppression status and location on cheek did not affect the risk of metastasis. Finally, poor differentiation (OR, 5.97; 95% CI, 1.82-19.62; P = 0.003), perineural invasion (OR, 6.64; 95% CI, 3.63-12.12; P < 0.001), and Breslow greater than 2 mm (OR, 3.42; 95% CI, 1.76-6.66; P < 0.001) were associated with an increased risk of disease-specific death, whereas diameter; immunosuppression status; and location on ear, lip, and temple did not affect the risk of disease-specific death. We found that differentiation, perineural invasion, depth, diameter, and location could affect the prognosis of cSCC. The potential role of other patient characteristics on the prognosis of cSCC should be identified in further large-scale prospective studies.
Topics: Head and Neck Neoplasms; Humans; Immunosuppression Therapy; Prognosis; Risk Factors; Skin Neoplasms; Squamous Cell Carcinoma of Head and Neck
PubMed: 32991600
DOI: 10.1371/journal.pone.0239586 -
Regional Anesthesia and Pain Medicine Sep 2020Hallux valgus repair is associated with moderate-to-severe postoperative pain. The aim of this systematic review was to assess the available literature and develop... (Review)
Review
Hallux valgus repair is associated with moderate-to-severe postoperative pain. The aim of this systematic review was to assess the available literature and develop recommendations for optimal pain management after hallux valgus repair. A systematic review using PROcedure SPECific Postoperative Pain ManagemenT (PROSPECT) methodology was undertaken. Randomized controlled trials (RCTs) published in the English language from inception of database to December 2019 assessing postoperative pain using analgesic, anesthetic, and surgical interventions were identified from MEDLINE, EMBASE, and Cochrane Database, among others. Of the 836 RCTs identified, 55 RCTs and 1 systematic review met our inclusion criteria. Interventions that improved postoperative pain relief included paracetamol and non-steroidal anti-inflammatory drugs or cyclo-oxygenase-2 selective inhibitors, systemic steroids, ankle block, and local anesthetic wound infiltration. Insufficient evidence was found for the use of gabapentinoids or wound infiltration with extended release bupivacaine or dexamethasone. Conflicting evidence was found for percutaneous chevron osteotomy. No evidence was found for homeopathic preparation, continuous local anesthetic wound infusion, clonidine and fentanyl as sciatic perineural adjuncts, bioabsorbable magnesium screws, and plaster slippers. No studies of sciatic nerve block met the inclusion criteria for PROSPECT methodology due to a wider scope of included surgical procedures or the lack of a control (no block) group. The analgesic regimen for hallux valgus repair should include, in the absence of contraindication, paracetamol and a non-steroidal anti-inflammatory drug or cyclo-oxygenase-2 selective inhibitor administered preoperatively or intraoperatively and continued postoperatively, along with systemic steroids, and postoperative opioids for rescue analgesia.
Topics: Analgesia; Hallux Valgus; Humans; Nerve Block; Pain Management; Pain, Postoperative
PubMed: 32595141
DOI: 10.1136/rapm-2020-101479